Effects of cyclosporine on immunologic mechanisms in psoriasis.
A major impetus for further investigation of cellular immunologic mechanisms in psoriasis has been the discovery that cyclosporine, a potent immunosuppressive, is highly effective in the treatment of psoriasis. Cyclosporine has significant inhibitory effects on the ability of T cells to become activated. However, a direct activity of this drug on human keratinocyte signal transduction or growth has been difficult to demonstrate at relevant concentrations. Nevertheless, treatment of psoriasis or of 12-O-tetradecanoyl phorbol-13-acetate-treated murine skin with cyclosporine does reverse many epidermal abnormalities that are common to these two systems. This suggests that the compound exerts an indirect effect on epidermal keratinocytes in vivo, perhaps through immunocyte inhibition. During treatment of psoriasis patients, cyclosporine therapy resulted in selective changes in the numbers and functions of certain antigen-presenting cell subsets (which were distinct from Langerhans cells) and T-cell subsets. These changes were accompanied by indirect evidence of decreased T-cell lymphokine release. Lesional activity of cyclosporine-treated psoriasis patients was closely correlated with the degree of T-cell activation caused by antigen-presenting cells. Cyclosporine inhibition of lymphokine or cytokine release may result in decreased recruitment of non-Langerhans antigen-presenting cells into the epidermis and thus decreased immunoreactivity in the lesion.
Cooper
K D
KD
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109.
Voorhees
J J
JJ
Fisher
G J
GJ
Chan
L S
LS
Gupta
A K
AK
Baadsgaard
O
O
D003524:Cyclosporins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015603:Keratinocytes / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D003524:Cyclosporins